crossing96/oncoscreening huggingface dataset:
Detection of Bladder Cancer in Urine Sediments by a Novel Multicolor Fluorescence In Situ Hybridization (Quartet) Test.	BACKGROUND: Bladder cancer is among the common human malignancies that show a heavy mutational load and copy number variations of numerous chromosomes, which makes them a target for diagnostic explorations. OBJECTIVE: We aimed to design a multicolor fluorescence in situ hybridization (FISH) test referred to as the quartet test for the detection of bladder cancer in urine. DESIGN, SETTING, AND PARTICIPANTS: We performed genome-wide copy number variation analysis on cohorts from the University of Texas MD Anderson Cancer Center (n=40) and The Cancer Genome Atlas (n=129), and identified the most frequently amplified chromosomal regions. These data were used to select four of the amplified regions to design a multicolor FISH test, referred to as the quartet test. Assay validation was performed on urine samples from 98 patients with bladder cancer: 56 with low-grade papillary, 42 with high-grade invasive disease, and 48 benign controls. INTERVENTION: The quartet test can be used in clinical practice for noninvasive detection of bladder cancer. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We initially analyzed samples using a fraction of abnormal cell scores and then by the quantitative score, which included not only the proportion of cells with abnormal copy numbers, but also the proportion of cells with numbers of altered copies and degree of amplification. We used receiver operator characteristic (ROC) curves to identify cutoff values for the scores at which performances of sensitivity and specificity were maximized. RESULTS AND LIMITATIONS: The copy number status assessed by probes detected in voided urine reflected the amplification status of the primary tumor. An ROC curve summarizing the proportion of assayed cells with any abnormal copy numbers gave specificity of 93.8% and sensitivity of 78.6% using the proportion of cells with abnormal copy numbers. The quantitative score giving extra weight to cells with multiple simultaneous amplifications provided 95.8% specificity and 76.8% sensitivity. Both percentage of abnormal cells and quantitative scores were highly effective for assessing the grade of the tumor. The full spectrum of potential clinical applications was not explored in the current study, and further validation studies are needed. CONCLUSIONS: The quartet test shows promising specificity and sensitivity results, but it requires validation on a larger multi-institutional cohort of samples. PATIENT SUMMARY: The quartet test can be used for noninvasive detection of bladder cancer in voided urine. It can also be used to assess the grade of the tumor and tumor recurrence as well as post-treatment effects.	bladder
Evaluation of two-dimensional ultrasonography and computed tomography in the mapping and measuring of canine urinary bladder tumors.	Determining the dimensions of transitional cell carcinomas (TCCs) of the urinary bladder in dogs is important in assessing tumor progression and the response to treatment. The primary aim of this study was to evaluate the reliability of a standardized two-dimensional (2-D) ultrasound (US) protocol performed by a single experienced operator. Secondary aims were to compare World Health Organization (WHO) and Response Evaluation Criteria in Solid Tumors (RECIST) guidelines, and to compare measurements by two operators following these guidelines. These were evaluated by inter-operator and intra-operator reliability using the concordance correlation coefficient (CCC) and Cohen's κ statistics, which demonstrated substantial to better agreement by an experienced operator using either set of guidelines. It was demonstrated that 2-D US provides a reliable means to determine the dimensions of urinary bladder TCC when an experienced operator used a standardized protocol. In a subset of dogs, urinary bladder distension was varied, which resulted in differences in measurement with 2-D US and computed tomography.	bladder
Atezolizumab (MPDL3280A) Monotherapy for Patients With Metastatic Urothelial Cancer: Long-term Outcomes From a Phase 1 Study.	IMPORTANCE: Atezolizumab (anti-programmed death ligand 1) has demonstrated safety and activity in advanced and metastatic urothelial carcinoma, but its long-term clinical profile remains unknown. OBJECTIVE: To report long-term clinical outcomes with atezolizumab therapy for patients with metastatic urothelial carcinoma. DESIGN, SETTING, AND PARTICIPANTS: Patients were enrolled in an expansion cohort of an ongoing, open-label, phase 1 study. Median follow-up was 37.8 months (range, >0.7 to 44.4 months). Enrollment occurred between March 2013 and August 2015 at US and European academic medical centers. Eligible patients had measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1, Eastern Cooperative Oncology Group performance status 0 to 1, and a representative tumor sample. Programmed death ligand 1 expression on immune cells was assessed (VENTANA SP142 assay). INTERVENTIONS: Atezolizumab was given intravenously every 3 weeks until unacceptable toxic effects, protocol nonadherence, or loss of clinical benefit. MAIN OUTCOMES AND MEASURES: Primary outcome was safety. Secondary outcomes included objective response rate, duration of response, and progression-free survival. Response and overall survival were assessed in key baseline subgroups. RESULTS: Ninety-five patients were evaluable (72 [76%] male; median age, 66 years [range, 36-89 years]). Forty-five (47%) received atezolizumab as third-line therapy or greater. Nine patients (9%) had a grade 3 to 4 treatment-related adverse event, mostly within the first treatment year; no serious related adverse events were observed thereafter. One patient (1%) discontinued treatment due to a related event. No treatment-related deaths occurred. Responses occurred in 26% (95% CI, 18%-36%) of patients. Median duration of response was 22.1 months (range, 2.8 to >41.0 months), and median progression-free survival was 2.7 months (95% CI, 1.4-4.3 months). Median overall survival was 10.1 months (95% CI, 7.3-17.0 months); 3-year OS rate was 27% (95% CI, 17%-36%). Response occurred in 40% (95% CI, 26%-55%; n = 40) and 11% (95% CI, 4%-25%; n = 44) of patients with programmed death ligand 1 expression of at least 5% tumor-infiltrating immune cells (IC2/3) or less than 5% (IC0/1), respectively. Median overall survival in patients with IC2/3 and IC0/1 was 14.6 months (95% CI, 9.0 months to not estimable) and 7.6 months (95% CI, 4.7 to 13.9 months), respectively. CONCLUSIONS AND RELEVANCE: Atezolizumab remained well tolerated and provided durable clinical benefit to a heavily pretreated metastatic urothelial carcinoma population in this long-term study. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01375842.	bladder
Bladder resident macrophages: Mucosal sentinels.	Macrophages are instrumental in the response to infectious and noninfectious diseases, however, their role in the bladder is poorly understood. Indeed, the bladder is a mucosal tissue frequently overlooked in research, despite the prevalence of illnesses such as urinary tract infection and bladder cancer. Notably, bladder tissue macrophages are among the most populous resident immune cells in this organ and recent studies support that resident macrophages and infiltrating monocytes play nonredundant roles in response to infection, immunotherapy, and inflammation. Advancing our understanding of macrophage behavior in the bladder is complicated by the difficulty in obtaining tissue-resident cells. Surmounting this challenge, however, for a greater understanding of macrophage ontology, impact on innate and adaptive immunity, and regulation of homeostasis, will ultimately contribute to better therapies for common afflictions of the bladder.	bladder
Puerarin Inhibits Proliferation and Induces Apoptosis by Upregulation of miR-16 in Bladder Cancer Cell Line T24.	Bladder cancer (BC) is a common disease of the urinary system. Puerarin is a flavonoid extracted from Pueraria lobata. However, the role of puerarin in BC remains unclear. Hence, this study aimed to investigate the effect of puerarin on BC cells. Cell viability, proliferation, and apoptosis were measured by CCK-8, BrdU assay, and flow cytometry analysis, respectively. The expressions of miR-16, apoptosis-related factors, and the main factors of the NF-κB pathway were analyzed by qRT-PCR and Western blot. In this study, we found that cell viability and proliferation were significantly reduced, cell apoptosis was enhanced, and the mRNA level of miR-16 was upregulated in puerarin-treated T24 cells. Further, silencing of miR-16 inhibited the decrease in cell viability and the increase in apoptosis. The expression of main factors involved in the NF-κB signaling pathway was downregulated in the puerarin group, while miR-16 silencing alleviated these downregulations. More importantly, puerarin deactivated the NF-κB signaling pathway via upregulation of miR-16. Also, miR-16 downregulated COX-2 expression via deactivation of the NF-κB signaling pathway. This study demonstrated that puerarin could inhibit cell proliferation, promote cell apoptosis, and deactivate NF-κB signaling pathway via upregulation of miR-16 in T24 cells.	bladder
Transcriptional and post-transcriptional upregulation of p27 mediates growth inhibition of isorhapontigenin (ISO) on human bladder cancer cells.	There are few approved drugs available for the treatment of muscle-invasive bladder cancer (MIBC). Recently, we have demonstrated that isorhapontigenin (ISO), a new derivative isolated from the Chinese herb Gnetum cleistostachyum, effectively induces cell-cycle arrest at the G0/G1 phase and inhibits anchorage-independent cell growth through the miR-137/Sp1/cyclin D1 axis in human MIBC cells. Herein, we found that treatment of bladder cancer (BC) cells with ISO resulted in a significant upregulation of p27, which was also observed in ISO-treated mouse BCs that were induced by N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN). Importantly, knockdown of p27 caused a decline in the ISO-induced G0-G1 growth arrest and reversed ISO suppression of anchorage-independent growth in BC cells. Mechanistic studies revealed that ISO promoted p27 expression at mRNA transcription level through increasing direct binding of forkhead box class O1 (FOXO1) to its promoter, while knockdown of FOXO1 attenuated ISO inhibition of BC cell growth. On the other hand, ISO upregulated the 3'-untranslated region (3'-UTR) activity of p27, which was accompanied by a reduction of miR-182 expression. In line with these observations, ectopic expression of miR-182 significantly blocked p27 3'-UTR activity, whereas mutation of the miR-182-binding site at p27 mRNA 3'-UTR effectively reversed this inhibition. Accordingly, ectopic expression of miR-182 also attenuated ISO upregulation of p27 expression and impaired ISO inhibition of BC cell growth. Our results not only provide novel insight into understanding of the underlying mechanism related to regulation of MIBC cell growth but also identify new roles and mechanisms underlying ISO inhibition of BC cell growth.	bladder
Immune checkpoint inhibitors for metastatic bladder cancer.	Chemotherapy has represented the standard therapy for unresectable or metastatic urothelial carcinoma for more than 20 years. The growing knowledge of the interaction between tumour and immune system has led to the advent of new classes of drugs, the immune-checkpoints inhibitors, which are intended to change the current scenario. To date, immunotherapy is able to improve the overall responses and survival. Moreover, thanks to its safety profile immune-checkpoint inhibitors could be proposed also to patients unfit for standard chemotherapy. No doubts that these agents have started a revolution expected for years, but despite this encouraging results it appears clear that not all subjects respond to these agents and requiring the development of reliable predictive response factors able to isolate patients who can more benefit from these treatments as well as new strategies aimed to improve immunotherapy clinical outcome. In this review we describe the active or ongoing clinical trials involving Programmed Death Ligand 1 (PD-L1), Programmed Death receptor 1 (PD-1) and Cytotoxic-T Lymphocyte Antigen 4 (CTLA 4) inhibitors in urothelial carcinoma focusing our attention on the developing new immune-agents and combination strategies with immune-checkpoint inhibitors.	bladder
Paraganglioma of the Urinary Bladder: A Rare Cause of Hypertension and Urinary Tract Infections.	Pheochromocytoma is a neoplasm, which develops from cells of the chromaffin tissues that are derived from the ectodermic neural system and mostly situated within the adrenal medulla. Approximately 15% of pheochromocytoma cases arise from extra-adrenal chromaffin tissue. Pheochromocytoma of the bladder is rare and accounts for less than 0.06% of all bladder neoplasms and less than 1% of all pheochromocytomas. We report a case of a young woman who presented with uncontrolled hypertension, recurrent urinary tract infections and micturition attacks and was found to have a metastatic bladder paraganglioma. In addition, we provide a summary table of the clinical manifestations of paragangliomas based on anatomic locations.	bladder
Implementing risk-aligned bladder cancer surveillance care.	Implementation science is a rapidly developing field dedicated to the scientific investigation of strategies to facilitate improvements in healthcare delivery. These strategies have been shown in several settings to lead to more complete and sustained change. In this essay, we discuss how refined surveillance recommendations for non-muscle-invasive bladder cancer, which involve a complex interplay between providers, healthcare facilities, and patients, could benefit from use of implementation strategies derived from the growing literature of implementation science. These surveillance recommendations are based on international consensus and indicate that the frequency of surveillance cystoscopy should be aligned with each patient's risk for recurrence and progression of disease. Risk-aligned surveillance entails cystoscopy at 3 and 12 months followed by annual surveillance for low-risk cancers, with surveillance every 3 months reserved for high-risk cancers. However, risk-aligned care is not the norm. Implementing risk-aligned surveillance could curtail overuse among low-risk patients, while curbing underuse among high-risk patients. Despite clear direction from respected and readily available clinical guidelines, there are multiple challenges to implementing risk-aligned surveillance in a busy clinical setting. Here, we describe how implementation science methods can be systematically used to understand determinants of care and to develop strategies to improve care. We discuss how the tailored implementation for chronic diseases framework can facilitate systematic assessment and how intervention mapping can be used to develop implementation strategies to improve care. Taken together, these implementation science methods can help facilitate practice transformation to improve risk-aligned surveillance for bladder cancer.	bladder
Efficacy and Tolerability of Bacillus Calmette-Guérin Therapy as the First-Line Therapy for Upper Urinary Tract Carcinoma In Situ.	There are few data on Bacillus Calmette-Guérin (BCG) therapy for upper urinary tract carcinoma in situ (UUT CIS). We retrospectively evaluated the efficacy and tolerability of BCG therapy for 41 patients [52 renal units(RUs)] with UUT CIS. Of 52 RUs, complete response was achieved in 47 (90%). The 5-year recurrence-, progression-free survival rates were 60.2% and 74.2%, respectively. Adverse events were observed in 31 (76%) patients, but most of them were mild. The scheduled instillations were completed in 31 (74%) of 42 patients. Our results demonstrated that BCG therapy for UUT CIS was satisfactory with high efficacy and tolerability.	bladder
B7-Homolog 4 Promotes Epithelial-Mesenchymal Transition and Invasion of Bladder Cancer Cells via Activation of Nuclear Factor-κB.	B7-homolog 4 (B7-H4), a member of the B7 family of costimulatory molecules, has been reported to be upregulated in urothelial cell carcinoma. This study was conducted to explore the biological role of B7-H4 in the aggressiveness of bladder cancer and the associated molecular mechanism. We found that the mRNA and protein levels of B7-H4 were significantly greater in bladder cancer cell lines than in SV-HUC-1 (normal human urothelial cells). Overexpression of B7-H4 significantly promoted bladder cancer cell migration and invasion, whereas knockdown of B7-H4 exerted an opposite effect. However, the growth of bladder cancer cells was not altered by B7-H4 overexpression or knockdown. Overexpression of B7-H4 promoted epithelial-mesenchymal transition (EMT), as evidenced by decreased E-cadherin and increased vimentin expression. The EMT inducers Twist1 and Snail were upregulated by B7-H4 overexpression and downregulated by B7-H4 silencing. Mechanistically, overexpression of B7-H4 induced the activation of NF-κB signaling. Pharmacological inhibition of NF-κB partially prevented B7-H4-mediated bladder cancer cell invasion. Taken together, B7-H4/NF-κB signaling is involved in the EMT and invasion of bladder cancer cells and represents a new candidate target for the treatment of bladder cancer.	bladder
Bladder cancer: detection and image quality compared among iShim, RESOLVE, and ss-EPI diffusion-weighted MR imaging with high b value at 3.0 T MRI.	To compare the detection of bladder neoplasms and image quality among the diffusion-weighted imaging (DWI) acquired by the prototype single-shot echo-planar-imaging (ss-EPI) sequence for integrated slice-specific dynamic shimming (iShim), readout segmentation of long variable echo trains (RESOLVE) and conventional ss-EPI sequences.Around 63 patients with 77 bladder lesions were enrolled. The MR protocol included T1WI, T2WI and 3 types of DWI. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of each DWI for the detection of bladder tumor were computed. The subjective scores of imaging quality, diagnostic confidence, and detection of tumors of stage T2 or greater were recorded. The contrast-to-noise ratio (CNR), signal intensity ratios, and apparent diffusion coefficient (ADC) values were measured. The univariate analysis of variance technique, the Friedman test, and Bland-Altman plots were used in the statistical analysis. Observer performance of tumor T stage was tested using receiver operating characteristic (ROC) curve analysis.The sensitivity, NPV, and accuracy of iShim (92.75%; 61.54%; 93.51%) for detection of bladder tumor were superior to those of RESOLVE (84.06%; 42.11%; 85.71%) and ss-EPI (86.96%; 47.06%; 88.31%). All qualitative scores of iShim were higher than RESOLVE (all P < .05) and ss-EPI (all P < .05). The CNR, signal intensity ratios between bladder lesion and urine, lesion, and submucosal stalk (or nearby normal bladder wall), and between distal normal bladder wall and urine of iShim (39.84 ± 12.11, 2.40 ± 0.60, 1.98 ± 0.43, 1.28 ± 0.16) were higher than RESOLVE (16.97 ± 7.08, 1.62 ± 0.41, 1.52 ± 0.42, 1.15 ± 0.29, all P < .05) and ss-EPI (27.89 ± 9.65, 1.66 ± 0.46, 1.57 ± 0.50, 0.99 ± 0.22, all P < .05). No significant difference of ADC values were found for iShim and RESOLVE (P=0.46), iShim, and ss-EPI (P = 0.97), RESOLVE and ss-EPI (P = .48). The Az value for the detection of tumors of stage T2 or greater was slightly higher with the iShim DWI sequence (0.89) than with the RESOLVE (0.87, P = 0.72) or ss-EPI (0.85, P = .38) sequence.The iShim DWI has relatively better detection of bladder tumor and image quality without significant ADC value difference.	bladder
The Activity of Class I-IV Alcohol Dehydrogenase Isoenzymes and Aldehyde Dehydrogenase in Bladder Cancer Cells.	OBJECTIVES: The aim of this study was to determine the differences in the activity of Alcohol Dehydrogenase (ADH) isoenzymes and Aldehyde Dehydrogenase (ALDH) in normal and cancerous bladder cells. METHODS: Class III, IV of ADH and total ADH activity were measured by the photometric method and class I, II ADH and ALDH activity by the fluorometric method. RESULTS: Significantly higher total activity of ADH was found in both, low-grade and high-grade bladder cancer, in comparison to healthy tissues. CONCLUSION: The increased activity of total ADH in bladder cancer cells may be the cause of metabolic disorders in cancer cells, which may intensify carcinogenesis.	bladder
Peptide-Mediated Targeting Mesoporous Silica Nanoparticles: A Novel Tool for Fighting Bladder Cancer.	Transitional cell carcinoma of the bladder is particularly devastating due to its high rate of recurrence and difficulty in retention of treatments within the bladder. Current cystoscopic approaches to detect and stage the tumor are limited by the penetrative depth of the cystoscope light source, and intravesical dyes that highlight tumors for surgical resection are non-specific. To address the needs for improved specificity in tumor detection and follow-up, we report on a novel technology relying on the engineered core of mesoporous silica (MSN) with surface modifications that generate contrast in fluorescence and magnetic resonance imaging (MRI). The particle surface was further functionalized to include a bladder cancer cell specific peptide, Cyc6, identified via phage display. This peptide possesses nanomolar specificity for bladder cancer cells and homology across multiple species including mouse, canine, and human. Our study takes advantage of its target expression in bladder tumor which is not expressed in normal bladder wall. When functionalized to MSN, the Cyc6 improved binding efficiency and specificity for bladder cancer cells in vitro. In an in vivo model, MSN instilled into bladders of tumor-bearing mice enhanced T 1- and T 2-weighted MRI signals, improving the detection of the tumor boundaries. These findings support the notion that our targeted nanomaterial presents new options for early detection and eventual therapeutic intervention. Ultimately, the combination of real-time and repeated MRI evaluation of the tumors enhanced by nanoparticle contrast have the potential for translation into human clinical studies for tumor staging, therapeutic monitoring, and drug delivery.	bladder
A Comprehensive Review of US FDA-Approved Immune Checkpoint Inhibitors in Urothelial Carcinoma.	Few effective treatment options are available for patients with advanced or metastatic urothelial carcinoma (UC) after unsuccessful first-line platinum-based chemotherapy. To date, immune checkpoint inhibitors are novel therapeutic agents for UC treatment. From May 2016 to May 2017, five anti-PD-1/PD-L1 monoclonal antibodies received accelerated or regular approval from the US Food and Drug Administration (FDA) for the treatment of patients with locally advanced or metastatic UC. The present comprehensive review presents the background information of these five US FDA-approved anticancer agents to provide a basic but concise understanding of these agents for advanced studies. We summarize their immune checkpoint mechanisms, clinical efficacy, recommended usage protocols, adverse events, and the limitations of the PD-L1 biomarker assays.	bladder